Heretofore, vehicles for rendering insoluble or sparingly soluble medicaments suitable for parenteral administration used, generally, one or a mixture of synthetic solubilizing agents such as propylene glycol, polyethylene glycols, various emulsifying agents such as those marketed under the tradenames Cremophor EL, Tweens and Pluronics. The latter group of solubilizing agents functions by the formation of a colloidal system (micelles). The synthetic solubilizing agents including the above-mentioned micelle forming agents can be disadvantageous in that, upon parenteral administration, they may cause side effects such as allergic reactions, anaphylactic shock, hemolysis and pyrogenic action.
In addition to the synthetic micelle-forming agents discussed above, there are natural micelle forming agents such as cholic acid and various derivatives thereof. These natural micelle forming agents are, however, ionic and, therefore, strongly lytic. They produce hemolysis and have accordingly not previously been considered for the preparation of compositions for parenteral administration.
U.S. Pat. No. 4,158,707 discloses that the disadvantageous lytic action of the cholic acid derivatives can be eliminated or substantially reduced by combining the cholic acid derivatives with certain pharmaceutically acceptable lipoids, e.g., phorphatidyl-cholines, glycerin ether phosphatides and phosphatidylethanolamines.
In addition, DOS No. 2,730,570 discloses aqueous solutions of insoluble or sparingly soluble medicaments, which are suitable for parenteral administration, wherein the micelle formers are gallic acid derivatives. The gallic acid derivatives, however, have a cholectic activity which is undesirable.